The major goal of this project will be to examine how methamphetamine (METH)-induced monoamine depletions affect basal ganglia-mediated learning and the expression of three molecules thought to be critically involved in learning and memory function (c-fos, zif268, arc) in the dorsal striatum. We hypothesize that METH-induced monoamine depletions will impair basal ganglia-mediated learning and alter the normal expression of molecules associated with synaptic plasticity in the dorsal striatum. The basic experimental design will be to treat rats with a neurotoxic regimen of METH, known to induce monoamine depletions in the basal ganglia. These METH-treated rats, along with controls, will then be trained on a basal gangliadependent motor-response learning task in a plus maze. Once the rats meet motor-response learning criterion, the brains will be removed and processed for in situ hybridization to identify c-fos, zif268, and arc mRNA expression in identified efferent neuron populations of the dorsal striatum. This work will lead to a better understanding of how METH abuse affects normal learning and memory function and will provide insight into how changes in brain chemistry induced by drugs of abuse might lead to drug addiction.